The invention concerns a DNP (dynamic nuclear polarization) apparatus comprising at least one cryostat having an opening and a loading path for loading the cryostat with a sample, wherein the loading path extends in a straight line from the opening to a sample receptacle at the location of the sample in the cryostat, wherein a magnet coil is arranged in the cryostat for generating a homogeneous magnetic field at the location of the sample during the measurement, wherein a microwave source is provided for generating microwave radiation, and wherein a configuration for supplying microwave radiation from the microwave source to the location of the sample is arranged in the cryostat, the configuration comprising a microwave path extending in a straight line directly from the opening to the location of the sample in the cryostat.
A configuration of this type is disclosed e.g. in WO 08/121458 A1 (reference [6]).
Nuclear magnetic resonance (NMR) spectroscopy is a method that is commercially widely used for characterizing the chemical composition of substances. The magnetic resonance imaging (MRI) method is based on the same basic physical principles as NMR spectroscopy. Both methods have the disadvantage that they are substantially insensitive since, even in strong magnetic fields, polarization of the atomic nuclei is very weak. For this reason, an increase in the signal-to-noise-ratio (SNR) is one of the most important aims in the development of NMR and MRI devices. The SNR can be increased either by reducing the noise portion or by increasing the signal level. The noise was reduced with great success in recent years by using cooled NMR and also MRI coils.
The desired increase in the NMR signal can be realized e.g. by using stronger NMR magnets which entails, however, considerable additional cost and in most cases also increased space requirements for the apparatus.
As an alternative, so-called “dynamic nuclear polarization” (DNP) methods may be used.
There are different experimental methods in the field of nuclear magnetic resonance spectroscopy, which significantly increase the nuclear polarization and thereby also increase the detection sensitivity of the experiment. One of these methods is dynamic nuclear polarization (DNP). This technology requires simultaneous irradiation of a magnetic microwave field at a frequency which is higher by a factor of 660 compared to the nuclear Larmor frequency of the 1H nuclei.
Dynamic nuclear polarization requires the presence of polarization agents in the sample, e.g. free radicals with unpaired electron spins. Moreover, one utilizes the fact that electrons achieve high polarization at low temperatures in a strong magnetic field. Transfer of the electron polarization to the atomic nuclei of the sample is effected through irradiation of a microwave field of a suitable frequency due to interactions. When the nuclear spins in the sample have reached a sufficiently high level of polarization, the sample can be quickly heated to room temperature by means of a dissolution liquid, e.g. hot water. This process must be performed within a sufficiently short time since the nuclear spins quickly lose their polarization at higher temperatures. The methods of polarization and subsequent heating and dissolving of the sample are disclosed e.g. in references [1], [2], [6] and [7].
In reference [1], the magnet coil is cooled in a magnet cryostat to temperatures in the range between 4 K and 4.5 K. The sample is directly introduced into the same magnet cryostat and cooled to 1 K to 5 K in a separate helium region within this cryostat. The electron spins are then excited by means of suitable microwave radiation. The frequency of the microwave radiation depends on the strength of the magnetic field in which the sample is located. It is in a range between 50 GHz and 1000 GHz.
The microwaves are introduced into the magnet cryostat through the same opening as the sample by means of a wave guide. The sample is introduced with a sample holder from the top into the magnet cryostat. Sample lines are moreover introduced from the top into the cryostat for dissolving the sample. Since the space in the cryostat is relatively small, the microwaves cannot be guided in a straight way to the sample but must be deflected by means of mirrors for irradiation. The microwaves are thereby attenuated which results in power losses.
Reference [3] discloses a DNP method in which, in contrast to reference [1], a sample cryostat is inserted into the magnet cryostat in the form of an insert. The sample is introduced into the sample cryostat and cooled to temperatures in the range between 1 K and 5 K. The cold sample is then also irradiated with high-frequency microwaves in order to excite the electron spins. In this configuration, the sample is initially irradiated using a microwave guide that is inserted in a straight line from the top. When the electron spins have reached an adequate level of polarization, the microwave guide is removed in an upward direction from the sample cryostat and a device for dissolving the sample is inserted from the top and moved to the sample. This configuration is advantageous in that the microwave guide can be straight, but is disadvantageous in that changing between the microwave guide and the sample dissolution device is complex. This change is very difficult to automate.
In a further development of reference [3], which is described in reference [4], a plurality of samples are simultaneously cooled in a sample cryostat. The samples are located in a sample changer which is designed as a rotary plate. In this device, the samples can be polarized at a circumferential position by means of the microwaves and the sample can be dissolved at a different circumferential position. This configuration consequently enables straight guidance of the microwaves. This configuration is disadvantageous in that the changing device is located in the very cold area of the sample cryostat. Mechanical movement at temperatures below 5 K is very complex to enact and is prone to malfunction.
In reference [6], the microwave guide is guided in a straight way either within the loading path from the top to the location of the sample or in a further embodiment described in reference [6], the microwave guide surrounds the straight loading path. For this reason, the microwave guide passes in a straight way from the top to the sample. Coupling the microwaves into the exterior microwave guide is a complex and difficult process which is accompanied by microwave losses. When, however, the microwaves are guided within the loading path, the microwave guide must be removed from the loading path each time a sample is loaded. This process, which is also described in reference [6], is disadvantageous in that it is difficult to automate.
Reference [7] utilizes a magnet with two homogeneous magnetic field regions. In the first region, microwave irradiation is performed and in the second region dissolution and NMR measurement are performed. In reference [7], the loading path is combined with a movable microwave guide. The sample is thereby filled into a small sample holder and the sample holder is directly connected to the long movable microwave guide. The sample located in the sample holder is irradiated with the microwave in the first homogeneous magnetic field region. When polarization has reached an adequate level, the sample is transferred to the second homogeneous magnetic field region.
The conventional configurations have in common that the microwaves are introduced in each case through the same cryostat opening as the samples.
The configurations described in references [1], [3] and [7] are primarily designed for manual DNP operation. In reference [1] the sample holder and the wave guide are horizontally offset with respect to each other. This is, however, only possible by deflecting the wave guide e.g. using mirrors. This deflection attenuates the microwaves and thereby reduces the efficiency of the system.
In references [3] and [6], the microwaves are inserted in a straight line from the top which consequently causes little loss. However, this is disadvantageous in that the wave guide must be removed prior to the dissolution step. It is then replaced by the dissolution device consisting of a solvent supply line and an outlet line. This procedure is disadvantageous in that it is difficult to automate.
In reference [7], the dissolution device is inserted from below, however, the microwave guidance must be removed each time a sample is loaded. This is very complex and automation is not possible. Furthermore, this construction requires a special cryostat design in which the sample and the microwave are introduced from one side and the dissolution device is introduced from the other side. In order to realize this, the cryostat has two openings which renders construction complicated and complex.
The configuration of reference [4] is disadvantageous in that it has a mechanical sample changer that must be operated at a temperature of less than 5 K. This mechanism is very complex and prone to malfunction.
In contrast thereto, it is the underlying purpose of the present invention to present a DNP apparatus of the above defined type which achieves simple and efficient polarization of the electron spins in the sample. The microwaves should thereby be guided in such a fashion that the losses on the way to the sample are minimized, thereby obtaining high efficiency. Moreover, the microwave guide should be permanently installed such that the microwaves do not need to be removed for changing the sample or during the dissolution step. The invention should moreover also enable highly reliable automation. Complicated mechanical devices at very low temperatures of less than 5 K should be absolutely prevented in this case. The space within the loading path in the cryostat shall be optimally utilized for loading and dissolving the sample.